Platelet activating factor (PAF) is a phospholipid released from human and other animal cells and is an acetylglyceryl ether of phosphorylcholine as represented by the following formula: ##STR1## where n is 15 or 17.
PAF is physiologically active and causes contraction of the airway smooth muscle, increased vascular permeability, platelet aggregation, hypotension and the like. It is now recognized as a powerful mediator of intimation and may play a physiological or pathobiologic role in a variety of clinical conditions, such as endotoxin- and IgG-induced shock (septic shock), asthma and pulmonary dysfunction, acute inflammation, transplanted organ rejection, thrombosis, cardiac anaphylaxis, gastrointestinal ulceration, allergic skin diseases, retinal and corneal diseases, chemically induced liver cirrhosis, and ovimplantation in pregnancy.
Several PAF antagonists have been reported (e.g., U.S. Pat. No. 4,948,795, European Patent Application EP 279681, and U.S. Pat. No. 4,786,645) but none have received wide acceptance. Therefore, there is a continuing need for the development of potent antagonists of PAF which have low toxicity.